crossing96/oncoscreening huggingface dataset:
FXR1 can bind with the CFIm25/CFIm68 complex and promote the progression of urothelial carcinoma of the bladder by stabilizing TRAF1 mRNA.	RNA-binding proteins (RBPs) are key regulators of gene expression. RBP dysregulation is reported to play essential roles in tumorigenesis. However, the role of RBPs in urothelial carcinoma of the bladder (UCB) is only starting to be unveiled. Here, we comprehensively assessed the mRNA expression landscape of 104 RBPs from two independent UCB cohorts, Sun Yat-sen University Cancer Center (SYSUCC) and The Cancer Genome Atlas (TCGA). Fragile X-related gene 1 (FXR1) was identified as a novel cancer driver gene in UCB. FXR1 overexpression was found to be related to the poor survival rate in the SYSUCC and TCGA cohorts. Functionally, FXR1 promotes UCB proliferation and tumorigenesis. Mechanistically, FXR1 serves as a platform to recruit CFIm25 and CFIm68, forming a novel 3' processing machinery that functions in sequence-specific poly(A) site recognition. FXR1 affects the 3' processing of Tumor necrosis factor receptor-associated factor 1 (TRAF1) mRNA, which leads to nuclear stabilization. The novel regulatory relationship between FXR1 and TRAF1 can enhance cell proliferation and suppress apoptosis. Our data collectively highlight the novel regulatory role of FXR1 in TRAF1 3' processing as an important determinant of UCB oncogenesis. Our study provides new insight into RBP function and provides a potential therapeutic target for UCB.	bladder
A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.	BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.	bladder
Baseline Health-related Quality of Life Predicts Bladder Cancer-specific Survival Following Radical Cystectomy.	BACKGROUND: It has been shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various metastatic cancers, but there is no evidence on the prognostic value of baseline HRQOL for patients with bladder cancer undergoing radical cystectomy (RC) and ileal conduit (IC) or orthotopic ileal neobladder (ONB) with curative intent. OBJECTIVE: To assess the association between baseline HRQOL and survival outcomes following RC. DESIGN, SETTING, AND PARTICIPANTS: The study included 407 patients with prospectively assessed baseline HRQOL before RC. Patients were stratified according to the Global Health Status (GHS) domain of the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, with good general HRQOL defined as GHS ≥70 on the basis of validated cutoff levels. A propensity score-matched analysis of 357 patients (1:2 ratio; 125 patients with GHS ≥70 vs 232 with GHS <70) was performed. INTERVENTION: RC with IC or ONB. OUTCOME MEASURES AND STATISTICAL ANALYSIS: The primary endpoint was cancer-specific survival (CSS). The secondary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier and multivariate Cox regression models were constructed to assess the prognostic value of baseline GHS for prediction of survival outcomes. RESULTS AND LIMITATIONS: Median follow-up was 40.5 mo. The rates of 5-yr CSS (82% vs 65%; p = 0.001), 5-yr OS (76% vs 53%; p = 0.001), and 5-yr RFS (50% vs 39%; p = 0.04) were significantly higher in the GHS ≥70 cohort. GHS ≥70 was confirmed as an independent predictor for CSS (hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.18-0.73; p = 0.004), OS (HR 0.45, 95% CI 0.26-0.79; p = 0.005), and RFS (HR 0.50, 95% CI 0.30-0.83; p = 0.008) in multivariate analyses. Study limitations include the retrospective analysis of prospectively collected data and use of a HRQOL questionnaire not specifically for bladder cancer. CONCLUSIONS: Our findings suggest that preoperative baseline HRQOL has significant predictive value for outcomes of RC with curative intent for bladder cancer. We found that good general HRQOL at baseline accurately predicts greater CSS, OS, and RFS. PATIENT SUMMARY: We assessed the association between health-related quality of life at baseline and survival outcomes after radical cystectomy for bladder cancer. We found that good general health-related quality of life at baseline predicts better survival outcomes and that higher baseline scores were associated with greater cancer-specific survival.	bladder
Acute renal failure and bladder tumors, about 106 cases.	OBJECTIVES: The overall objective of the study was to determine the prevalence of acute renal failure due to bladder tumors by describing the clinical, paraclinical, therapeutic, histological and clinical evolution parameters. MATERIALS AND METHODS: Retrospective study over a period of 2 years dating from the first of September 2017 to the 31 of October 2019 on a number of patients with acute renal failure due to bladder tumors treated at the department of urology in the Ibn Roch teaching Hospital in Casablanca. RESULTS: In a series of 597 cases of bladder tumors, the prevalence of acute renal failure was 17.8%. The mean age was 69.5 years [51-88], with a male predominance (97%). The main clinical signs were hematuria (87%), lower back pain (62%), oligo-anuria (31%) and acute urine retention (12%). The mean serum creatinine on admission was 1316μmol/L (extremes: 155-2477) and The mean serum urea was 2.4g/L (0.8-4). Renal ultrasound showed hydronephrosis in 96% of cases, which was bilateral in 69% of cases. Hemodialysis was indicated in 23.6% of the cases, due to hyperkalemia (14.1%), metabolic acidosis (6.6%) and acute pulmonary oedema in (2.8%). Percutaneous nephrostomy was performed in 77% of cases, bladder catheterization in 21% of cases and double J-stenting in 2% of cases. As to the treatment of bladder tumors, endoscopic trans-urethral bladder resection was the main treatment and was performed in (71%) of cases. Meanwhile, 21% of the patients benefited from a cystoprostatectomy and combined radio-chemotherapy was indicated in 9% of cases. The main histological finding was transitional cell carcinoma (98%). The evolution of renal function was favorable in 87% of cases. CONCLUSION: Acute renal failure is a frequent and severe complication of bladder tumors that can be life-threatening and makes it difficult to treat bladder tumors requiring multidisciplinary management.	bladder
Yolk sac differentiation in urothelial carcinoma - A rare variant originating from aberrant differentiation of sarcomatoid components.	Yolk sac differentiation occurs in somatic neoplasms of the gastrointestinal and gynecologic tracts; it has rarely been reported in urothelial carcinoma. Here, we report three cases of yolk sac differentiation in sarcomatoid urothelial carcinoma. The epithelioid component of the sarcomatoid urothelial carcinoma showed divergent differentiation, including squamous, conventional glandular, small cell carcinoma, and yolk sac components. The sarcomatoid component showed malignant spindle cells admixed with focal chondroid and rhabdoid elements. In all three cases, the yolk sac areas were admixed with the sarcomatoid component and showed a glandular pattern, with vacuolated, eosinophilic cytoplasm. These areas were positive for SALL4, variably positive for glypican 3 and AFP, and negative for the conventional urothelial markers GATA3, p63, and 34βE12. Yolk sac differentiation is an extremely rare occurrence in sarcomatoid urothelial carcinoma.	bladder
Immunotherapy versus chemotherapy as first-line treatment for advanced urothelial cancer: A systematic review and meta-analysis.	BACKGROUND: Pembrolizumab and atezolizumab have recently been approved for the first-line treatment of patients with advanced urothelial carcinoma (aUC) who are not eligible for cisplatin-based chemotherapy and whose tumors have high PD-L1 expression; however, the use of these immunotherapeutic agents relative to standard of care chemotherapy has ongoing concerns. The aim of this present study is to compare the effectiveness of single-agent immune-oncology (IO) compounds versus platinum-based chemotherapy in the first-line setting of aUC. METHODS: A comprehensive search for phase III trials on IO versus chemotherapy was conducted in PubMed, EMBASE, Web of Science, and Scopus databases from 01/2016 to 05/2021. An algorithm to obtain survival data from published Kaplan-Meier curves was used to reconstruct overall survival (OS) data. After demonstrating violation of the proportional hazard assumption, we used the difference in restricted mean survival time (ΔRMST) to compare OS. RESULTS: OS data from 2,068 individuals from 3 phase III trials investigating the role of IO vs chemotherapy were reconciled. Overall, patients receiving IO [n = 1,013 (49%)] or chemotherapy [n = 1,055 (51%)] had similar OS with a 24-month ΔRMST of -0.4 (95% CI: -1.1, 0.4; p = 0.2) months. In the cisplatin-ineligible population, patients receiving IO [n = 509 (49%)] or chemotherapy [n = 530 (51%)] had similar OS with a 24-month ΔRMST of 0.1 (95% CI: -0.9, 1.2; p = 0.7) months. In the cisplatin-ineligible population with PD-L1-high tumors, patients receiving IO [n = 226 (50%)] or chemotherapy [n = 226 (50%)] had similar OS with a 24-month ΔRMST of 1.1 (95% CI: -0.5, 2.7; p = 0.1) months. CONCLUSION: We found no OS benefit for patients treated with first-line immune checkpoint inhibition compared to chemotherapy among the overall population, cisplatin-ineligible patients, and PD-L1-high patients.	bladder
Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort: the ELAPSE project.	BACKGROUND: The evidence linking ambient air pollution to bladder cancer is limited and mixed. METHODS: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM(2.5)), nitrogen dioxide (NO(2)), black carbon (BC), warm season ozone (O(3)) and eight PM(2.5) elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders. RESULTS: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM(2.5) and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93-1.27) per 5 µg/m(3) for 2010 exposure and 1.06 (95% CI: 0.99-1.14) for baseline exposure. Effect estimates for NO(2), BC and O(3) were close to unity. A positive association was observed with PM(2.5) zinc (HR 1.08; 95% CI: 1.00-1.16 per 10 ng/m(3)). CONCLUSIONS: We found suggestive evidence of an association between long-term PM(2.5) mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM(2.5) suggests the importance of industrial emissions.	bladder
Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer.	In addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits more potent signatures of trained immunity including higher pro-inflammatory cytokine responses, greater myeloid cell reprogramming toward inflammatory and activated states, and enhances epigenetic and metabolomic changes. In a model of bladder cancer, we also show that re-engineered BCG induces trained immunity and improved functionality. These results indicate that trained immunity levels and antitumor efficacy may be increased by modifying BCG to express higher levels of key PAMP molecules.	bladder
CD103(+)CD8(+) tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer.	BACKGROUND: CD103(+)CD8(+) tissue-resident memory T (T(RM)) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT). METHODS: Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103(+)CD8(+) T(RM) cells. RESULTS: Patients with high CD103(+)CD8(+) T(RM) cells infiltration, but not CD8(+) T cells, are more likely to benefit from immunotherapy and ACT. The presence of T(RM) cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103(+)CD8(+) T(RM) cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients. CONCLUSIONS: CD103(+)CD8(+) T(RM) cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.	bladder
Identifying a Novel Defined Pyroptosis-Associated Long Noncoding RNA Signature Contributes to Predicting Prognosis and Tumor Microenvironment of Bladder Cancer.	BACKGROUND: Bladder cancer (BLCA) is a common malignant tumor of the urinary tract, which is the sixth most common cancer among men. Numerous studies suggested that pyroptosis and long noncoding RNAs (lncRNAs) played an essential role in the development of cancers. However, the role of pyroptosis-related lncRNAs in BLCA and their prognostic value are still unclear. METHODS: In this study, we constructed a signature model through least absolute shrinkage and selection operator (LASSO) Cox regression analysis and Cox univariate analysis based on The Cancer Genome Atlas (TCGA) database. The expression of 12 pyroptosis-related lncRNAs was also confirmed by qRT-PCR in BLCA cell lines. TIMER, XCELL, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT R script were applied to quantify the relative proportions of infiltrating immune cells. Correlation coefficients were computed by Spearman analyses. The Kaplan-Meier method, Cox regression model, and log-rank tests were used to evaluate the prognostic value. The R package of pRRophetic was used to predict IC50 of common chemotherapeutic agents. RESULTS: A total of 12 pyroptosis-related lncRNAs with great prognosis value were identified. The expression was investigated by qRT-PCR in four BLCA cell lines. Then, 126 cases were identified as high-risk group, and 277 cases were identified as low-risk group based on the cutoff point. Patients in the low-risk group showed a significant survival advantage. Furthermore, we found that clinical features were significantly related to the risk score. As well, based on the C-index values, a nomogram was constructed. The gene set enrichment analysis (GSEA) results showed that mitogen-activated protein kinase (MAPK) signaling, transforming growth factor (TGF)-β signaling, and WNT signaling were with important significance in the high-risk group. Moreover, we found that riskscore was positively correlated with M0 macrophages and M2 macrophages. CONCLUSIONS: In conclusion, our study indicated that pyroptosis is closely connected to BLCA. The riskscore generated from the expression of 12 pyroptosis-related lncRNAs was evaluated by various clinical features including survival status, tumor microenvironment, clinicopathological characteristic, and chemotherapy. It may offer a significant basis for future studies.	bladder
Continent cutaneous urinary diversion with an ileal pouch with the Mitrofanoff principle versus a Miami pouch in patients undergoing cystectomy for bladder cancer: results of a comparative study.	PURPOSE: Radical cystectomy (RC) is currently the standard of care for non-metastatic muscle invasive bladder cancer. Few studies compare methods of cutaneous continent urinary diversion (CCUD) following RC. The objective was to compare perioperative morbidity and functional outcomes of CCUD using an ileal pouch with a Mitrofanoff efferent versus a Miami ileocolic pouch in patients undergoing cystectomy of pelvic exenteration for bladder cancer. METHODS: This retrospective two-centre study included all consecutive patients who underwent radical cystectomy or pelvic exenteration with CCUD for bladder cancer between 2001 and 2020 in two academic French hospitals with a median follow-up time of 5.4 years. Patients were divided into two groups according to the type of urinary diversion: Miami ileocolonic pouch (group A) and ileal pouch with Mitrofanoff/Monti principle (group B). Continence rate, ability to perform intermittent self-catheterisation, complications and health-related quality of life (HRQoL) measured by the bladder cancer index were evaluated. RESULTS: Thirty-one patients were included. Continence was achieved in 11 out of 14 patients (79%) in group A versus 12 out of 17 patients (71%) in group B (P = 0.3). A significantly higher rate of cutaneous tube stenosis was reported in group B compared to group A (eight (47%) vs. one (7%) patient, respectively; P = 0.02). HRQoL outcomes were similar in both groups except less digestive discomfort observed in group A. CONCLUSIONS: When comparing the ileal pouch with Mitrofanoff/Monti's principle with a Miami pouch, no significant differences were found regarding continence rate, ability to self-catheterise, long-term complication rate and overall patient satisfaction.	bladder
P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer.	PURPOSE: The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis. METHODS: RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis. RESULTS: P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04). CONCLUSIONS: The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.	bladder
Impact of carcinoma in situ on the outcome of intravesical Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer: a comparative analysis of large real-world data.	BACKGROUND: This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression. RESULTS: At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression. CONCLUSION: Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.	bladder